MRSA infection Brijesh Singh Yadav brijeshbioinfo@gmail.com

Disease Type: Bacterial DiseaseCommon Name: Community-acquired MRSA (CA-MRSA); Hospital-acquired MRSA (HA-MRSA)Causative Agent: strain of Staphylococcus aureusDisease Discription: Methicillin-resistant Staphylococcus aureus (MRSA) is an infection caused by a strain of Staphylococcus aureus (S. aureus) bacteria that is highly resistant to antibiotics.(2) . Most MRSA infections occur in hospitals or other health care settings, such as nursing homes and dialysis centers. It's known as health care-associated MRSA, or HA-MRSA. Older adults and people with weakened immune systems are at most risk of HA-MRSA. More recently, another type of MRSA has occurred among otherwise healthy people in the wider community. This form, community-associated MRSA, or CA-MRSA, is responsible for serious skin and soft tissue infections and for a serious form of pneumonia. (4)

Fig. MRSA infection on skin

Causes of Disease:

S. aureus (“staph”) is a common bacteria that normally lives on the skin and sometimes in the nasal passages. MRSA refers to S. aureus strains that do not respond to the antibiotics normally used to cure staph infections.

The bacteria can cause infection when it enters the body through a cut, sore, catheter, or breathing tube. The infection can be minor and local (for example, a pimple), or more serious (involving the heart or bone).

Serious staph infections are more common in people with weak immune systems, usually patients in hospitals and long-term care facilities and those receiving kidney dialysis.(2)

Antibiotics have been in use for many years as a successfull treatment and cure for staph infections. However, these antibiotics have been overused, misused and over prescribed as a cure for staph aureus infection for many years. It is fairly common for people to not complete a course of antibiotics, or not use as prescribed. If this happens, it is probable that not 100% of the bacterium that caused staph infection will have been killed. Surviving staph bacterium develop a resistance to this antibiotic and multiply. As more and more antibiotics are prescribed, the number of staph bacterium that are able to resist those antibiotics become more numerous. The biggest problem with the use of antibiotics, is that they are non-focused. Therefore, they do not discriminate between good and bad bacterium, otherwise known as 'Flora' which can be found in the large intestines and form a large part of the bodies immune system. Without this immune system protection, 'superbugs' are free to develop.(1)

Risk Factors: People with higher risk of MRSA infection are those with obvious skin breaks (surgical patients, hospital patients with intravenous lines, burns, or skin ulcers) and patients with depressed immune systems (infants, elderly, or HIV-infected individuals) or chronic diseases (diabetes or cancer). Patients with pneumonia (lung infection) due to MRSA can transmit MRSA by airborne droplets. Health-care workers as a group are repeatedly exposed to MRSA-positive patients and can have a high rate of infection if precautions are not taken. Health-care workers and patient visitors should use disposable masks, gowns, and gloves when they enter the MRSA-infected patient's room.(5)

Causative Agent Description:Pathogen Name: Methicillin-resistant Staphylococcus aureus

Fig. Electron micrograph of MRSA

Pathogen Description: Staphylococcus aureus is a species of bacterium commonly found on the skin and/or in the noses of healthy people. Although it is usually harmless at these sites, it may occasionally get into the body (eg through breaks in the skin such as abrasions, cuts, wounds, surgical incisions or indwelling catheters) and cause infections. These infections may be mild (eg pimples or boils) or serious (eg infection of the bloodstream, bones or joints)(3).MRSA is resistant to (unable to be killed by) all beta-lactam antibiotics. This includes all penicillins (e.g., amoxicillin) and cephalosporins (e.g., keflex).

Taxonoimic Classification:

Domain BacteriaKingdom BacteriaPhylum FirmicutesClass BacilliOrder BacillalesFamily StaphylococcaceaeGenus StaphylococcusSpecies S.aureus

S.aureus Fig. A magnification of MRSA superbug(20,000 times)

Other Pathogenic speices: Borderline-resistant S. Aureus (BORSA), Western Samoan phage-pattern methicillin-resistant (10), Staphylococcus epidermidis, Staphylococcus aureus, S lugdunensis, S haemolyticus, S warneri, S schleiferi, S intermedius

Morphology and toxin production:

Blood agar plates (1A-C) showing the the normal phenotype (1A) and SCV phenotype (1C) of S. aureus; SCVs showing auxotrophism for hemin on chemically defined medium (2); electron micrographs showing the intracellular persistence of S. aureus SCVs within viable HaCaT cells (3a, b) versus severe lytic degeneration and release of bacteria in host cells infected with the normal S. aureus phenotype (3c, d); scanning electron microscopy showing cells of “fried-egg” SCVs (4); and transmission electron microscopy showing incomplete or multiple cross walls of SCVs (5);

Mechanisms of antibiotic resistance in Staphylococcus aureus biofilms and treatment and prevention of biofilms

Staphylococcus aureus causes severe infections with high morbidity and mortality. Additionally, this pathogen often forms biofilms that adhere to biomedical materials. The sessile bacteria that grow in biofilms show a 1000 to 1500 fold reduced sensitivity to antibiotics. The mechanism of biofilm resistance to antimicrobial agents is not yet clear, but it might depend on slow growth, induction of stress responses or a "biofilm phenotype". On the other hand the physical or chemical structure of the excreted polymers may shield the bacteria from the antibiotics. The elucidation of these biochemical and genetic mechanisms will yield new targets for the development of novel chemotherapeutic agents. Besides, the prevention of biofilm formation will enable existing antibiotics to successfully combat S. aureus infections.

History: Shortly after the introduction in 1959 of methicillin, a semisynthetic beta-lactamase resistant penicillin, isolates resistant to this agent were reported. Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) infections occurred in Europe in the early 1960s(12)

Methicillin was introduced in 1959 to treat infections caused by penicillin-resistant Staphylococcus aureus. In 1961 there were reports from the United Kingdom of S. aureus isolates that had acquired resistance to methicillin (methicillin-resistant S. aureus, MRSA) (1), and MRSA isolates were soon recovered from other European countries, and later from Japan, Australia, and the United States. MRSA is now a problem in hospitals worldwide and is increasingly recovered from nursing homes and the community.(13)

The first documented MRSA outbreak in the United States occurred at a Boston hospital in 1968. For the next two decades most MRSA infections occurred in persons who had contact with hospitals or other healthcare settings (healthcare-associated MRSA). However, MRSA infections are now seen in previously healthy persons. These persons appear to have acquired their infections in the community (community-associated MRSA), rather than in a healthcare setting. (14)

Epidemiology: Methicillin resistant Staphylococcus aureus (MRSA) has been the most clinically important nosocomial pathogen for the last 45 years; during which time the pathogen has gained resistance to all staphylococcal antibiotics including vancomycin. Unexpectedly, the epidemiology of MRSA changed with the millennium and this hospital-restricted pathogen has now aggressively spread in the community. Newly evolved MRSA strains have been reported in Australia, Europe, and across the United States and on each continent a predominant clone has emerged. The U.S. has observed the remarkable transmission of USA300, a clone that has caused an inordinate number of soft tissue infections in healthy pediatric and adult populations. Common among these clones is the

presence of the Panton-Valentine Leukocidin (PVL) and this association has been linked to virulence.(7)

Disease Host:Human

Disease Transmission: There are two major ways people become infected with MRSA. The first is physical contact with someone who is either infected or is a carrier (people who are not infected but are colonized with the bacteria on their body) of MRSA. The second way is for people to physically contact MRSA on any objects such as door handles, floors, sinks, or towels that have been touched by an MRSA-infected person or carrier. Normal skin tissue in people usually does not allow MRSA infection to develop; however, if there are cuts, abrasions, or other skin flaws such as psoriasis (chronic skin disease with dry patches, redness, and scaly skin), MRSA may proliferate. Many otherwise healthy individuals, especially children and young adults, do not notice small skin imperfections or scrapes and may be lax in taking precautions about skin contacts. This is the likely reason MRSA outbreaks occur in diverse types of people such as school team players (like football players or wrestlers), dormitory residents, and armed-services personnel in constant close contact.(5)

Mechanism: Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in community hospitals, long-term-care facilities, and tertiary care hospitals. The basic mechanism of resistance is alteration in penicillin-binding proteins of the organism.(11)

the role of different virulence factors in the development of staphylococcal infections remains incompletely understood. Some clonal types are well equipped to cause disease across the globe, whereas others are facile at causing disease among community members.

Signs and symptoms of disease:

Sometimes the bacteria remain confined to the skin. But they can also penetrate into the body, causing potentially life-threatening infections in bones, joints, surgical wounds, the bloodstream, heart valves and lungs. (4)

Most MRSA infections are skin infections that produce the following signs and symptoms:

o Cellulites (infection of the skin or the fat and tissues that lie immediately beneath the skin, usually starting as small red bumps in the skin).

o Boils (pus-filled infections of hair follicles),

o Abscesses (collections of pus in under the skin),

o Sty (infection of eyelid gland),

o Carbuncles (infections larger than an abscess, usually with several openings to the skin),

o Impetigo (a skin infection with pus-filled blisters). (5)

Diagnosis:

A skin sample ,pus on the skin, or blood, urine, or biopsy material (tissue sample) is sent to a microbiology lab and cultured for S. aureus. If S. aureus is isolated (grown on a Petri plate), the bacteria are then exposed to different antibiotics including methicillin. S. aureus that grows well when methicillin is in the culture are termed MRSA, and the patient is diagnosed as MRSA-infected. The same procedure is done to determine if someone is an MRSA carrier (screening for a carrier), but sample skin or mucous membrane sites are only swabbed, not biopsied.

In 2008, the U.S. Food and Drug Administration (FDA) approved a rapid blood test that can detect the presence of MRSA genetic material in a blood sample in as little as two hours. The test is also able to determine whether the genetic material is from MRSA or from less dangerous Staph bacteria. The test is not recommended for use in monitoring

treatment of MRSA infections and should not be used as the only basis for the diagnosis of a MRSA infection.(5)

Treatment:

Antibiotic therapy is still the mainstay of medical care for MRSA, but antibiotic therapy is complicated by MRSA's antibiotic resistance. Consequently, laboratory determination of MRSA antibiotic resistance and susceptibility is important to establishing effective antibiotic treatment. Definitive antibiotic therapy depends on using those antibiotics shown in microbiological tests (using Kirby-Bauer antibiotic discs on agar plates) to effectively reduce and stop MRSA growth. Once the antibiotic sensitivities of the patient sample are determined, the patient can be treated appropriately. Unfortunately, these tests take time (usually several days) before results are available.

The majority of serious MRSA infections are treated with two or more intravenous antibiotics that, in combination, often still are effective against MRSA (for example, vancomycin, linezolid, rifampin, sulfamethoxazole-trimethoprim, and others). Minor skin infections, however, may respond well to mupirocin (Bactroban). The earlier the appropriate diagnosis and therapy is instituted for MRSA, the better the prognosis.

Drainage of pus is the main surgical treatment of MRSA infections. Items that can serve as sources of infection (tampons, intravenous lines) should be removed. Other foreign bodies present that are likely sources of infection (for example, artificial grafts, artificial heart valves, or pacemakers) may need to be removed if appropriate antibiotic therapy is unsuccessful. Other areas that can harbor MRSA and may need surgical interventions are

joint infections, postoperative abscesses, and osteomyelitis. This is not an all-inclusive list; any site that continues to harbor and seed MRSA into the patient and is not adequately treated by antibiotic therapy should be considered for surgical intervention. Drainage of pus needs to be followed by appropriate antibiotic therapy as discussed above.(9)

Prevention:

Careful attention to personal hygiene is key to avoiding MRSA infections.

Wash your hands frequently, especially if visiting someone in a hospital or long-term care facility.

Make sure all doctors, nurses, and other healthcare providers wash their hands before examining you.

Do not share personal items such as towels or razors with another person -- MRSA can be transmitted through contaminated items.

Cover all wounds with a clean bandage, and avoid contact with other people’s soiled bandages.

If you share sporting equipment, clean it first with antiseptic solution. Avoid common whirlpools or saunas if another participant has an open lesion. Ensure that communal bathing facilities are clean(2)

Geographical Distribution: MRSA is a major nosocomial pathogen thatCauses severe morbidity and mortality worldwide.

Disease Statistics: A patient with a hospital-acquired infection is about 7 times more likely to die

than an uninfected patient. Latest data from the UK Department of Health and the Health Protection Agency

show that reports of MRSA have increased by 3.6% in England over the last year. Reports of blood-stream infections caused by MRSA have increased from 7,384

in 2002/03 to 7,647 in 2003/04. This represents a 3.6% increase during the last year.

However the total number of S. aureus infections (both methicillin-sensitive and methicillin-resistant) has increased and the number of blood stream infections caused by methicillin sensitive strains increased by 9.2% from 10,683 in 2002/0303 to 11,664 in 2003/04.(6)

Approximately 1-2% of people carry MRSA on their skin or in their nose.(8)

In 2006, 3,653 cases of MRSA infection were reported to MDH by the 12 sentinel hospital laboratories. Forty-one percent (1,502/3,653) of these cases were classified as CA-MRSA; 57% (2,077/3,653) were classified as HA-MRSA; and 2% (74/3,653) could not be classified (14)

The male-to-female ratio of skeletal infections is 2:1, mostly because boys are more likely to experience traumatic events.(9)

Fig. Hospital stays for MRSA staph infections 1993 though 2005

Source: Senior journal- health & medicine

Sources:1. MRSA Medical, UK2. Medline plus, a service by NIH & NLM, USA3. NetDoctor, UK4. Mayoclinic5. MedicineNet6. NHS7. MRSA resources, North America8. Virginia Dept of Health9. eMedicine Health10. ESR new Zealand11. Pubmed12. Benner, EJ, Kayser, FH. Growing clinical significance of methcillin-resistant

Staphylococcus aureus. Lancet 1968; 2:741. 13. National Academy of Sciences14. Minnesota department of Health brijeshbioinfo@gmail.com